Current cancer therapies have limited efficacy because they are highly toxic, ineffectively target tumors, and poorly penetrate tumor tissue. Engineered nanoparticles have the unique potential to overcome these limitations by actively targeting all tumor regions and delivering therapeutic payloads.
A large body of work is dedicated to developing nanocarriers that can carry a drug payload to a target tumor and deliver this payload on a stimulus. However, it is well known that such nanocarriers that utilize the vasculature for transport may not reach the hypoxic region of the tumors which have little or poorly developed vasculature. On the other hand, nanocarriers bounded to bacteria can use the mechanism of chemotaxis, preferred growth and hypoxic germination to target mainly hypoxic regions. However, since non-hypoxic tumor compartments may not secrete specific chemoreceptors that these bacteria may bind to, such areas won't get adequate cytotoxin. Likewise, non-hypoxic regions are not favorable places for bacteria to proliferate. Further, utilizing chemotaxis as a means of transport requires tailoring each bacterium for a specific type of cancer cell, thus limiting its broader appeal.
To alleviate such limitations, a system of a mixture of nanoparticles can be delivered via the vasculature. In tumor compartments with adequate vasculature, the non-bacteria linked nanocarriers will be delivered by the usual mechanism of diffusion. For tumor compartments, the active transport mechanism of bacteria that seek anaerobic microenvironments for growth will carry the nanoparticles. For such a mixture to be an effective treatment and to minimize systemic toxicity, precise control of the time and location of the nanoparticles is crucial.